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Jeewan S Titiyal,1 Samar K Basak,2 Naren Shetty,3 Umang Mathur,4 Prema Padmanabhan,5 Sri Ganesh,6 Arindam Dey,7 Dandapani Ramamurthy8 1Department of Cornea and Refractive Surgery, All India Institute of Medical Sciences, New Delhi, India; 2Department of Cornea and Cataract Services, Disha Eye Hospitals, Kolkata, India; 3Department of Cataract and Refractive Services, Narayana Nethralaya, Bengaluru, India; 4Department of Ophthalmology, Dr. Shroff’s Charity Eye Hospital, New Delhi, India; 5Department of Ophthalmology, Sankara Nethralaya, Chennai, India; 6Department of Phaco and Refractive Surgery, Nethradhama Superspeciality Eye Hospital, Bengaluru, India; 7Alcon Laboratories (India) Private Ltd, Bengaluru, India; 8Department of Cornea, Cataract and Refractive Services, The Eye Foundation, Coimbatore, IndiaCorrespondence: Jeewan S Titiyal, Department of Cornea and Refractive Surgery, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India, Email titiyal@gmail.comPurpose: To assess real-world clinical outcomes and safety of the Clareon® intraocular lens (IOL) and AutonoMe® automated preloaded delivery system in an Indian population.Patients and methods: This was a prospective, single-arm, multicenter, 12-month clinical study in patients aged ≥ 20 years with unilateral or bilateral cataracts. Surgery was performed by phacoemulsification followed by implantation of the Clareon monofocal IOL (CNA0T0). Monocular best-corrected distance visual acuity (BCDVA) and uncorrected distance visual acuity (UCDVA) were assessed at 1 week and 1, 6, and 12 months after implantation. Posterior capsular opacification (PCO), surface haze, and glistenings were evaluated at all visits. Surgeons’ satisfaction with automated injector system was also evaluated using a questionnaire. Safety was assessed by monitoring adverse events (AEs).Results: A total of 151 eyes received the CNA0T0 IOL. Mean ± SD monocular BCDVA improved from 0.53± 0.44 logMAR preoperatively to 0.00± 0.08 logMAR at week 1 and − 0.03± 0.08 logMAR at 12 months after implantation. At 12 months, 137/137 (100%) of eyes achieved BCDVA of 0.3 logMAR or better. Mean ± SD monocular UCDVA was 0.78± 0.40 logMAR preoperatively, 0.11± 0.15 logMAR at week 1, and 0.08± 0.13 logMAR at 12 months after implantation. At 12 months, 132/137 (96%) eyes achieved UCDVA of 0.3 logMAR or better. Serious intraoperative AEs were posterior capsule rupture (n=1) and ciliary zonular dehiscence (n=1). Surgeons reported that the automated preloaded device was more intuitive compared with other push- or screw-style preloaded injector systems. None of the eyes in this study presented surface haze; all were graded as 0 glistenings at all visits. No clinically significant PCO or neodymium-doped yttrium aluminum garnet (Nd:YAG) capsulotomies were reported.Conclusion: The hydrophobic IOL preloaded in an automated injector system provided good visual and refractive outcomes, as well as no surface haze and grade 0 glistenings. None of the patients required Nd:YAG capsulotomy.Keywords: glistenings, posterior capsular opacification, visual acuity

Recombinant adenoviral vectors (AdV) have been used experimentally as vaccines to present antigenic transgenes in vivo. However, administration of first-generation vectors (FG-AdV) is often limited by their induction of antiviral immunity. To address this limitation, helper-dependent vectors (HD-AdV) were developed that lack viral coding regions. While the administration of HD-AdV results in long-term gene expression in vivo, their utility as immunogens has never been examined. Direct vaccination with 108 blue- forming units (BFU) of HD-AdV injected into C57BL/6 mice lead to superior transgene-specific CTL and antibody responses when compared to the same amount of a FG-AdV. The antibody responses to viral antigens were high in response to both the vectors. As a mechanism to reduce viral exposure, dendritic cells (DC) were transduced with HD-AdV in vitro and then used as a cell-based vaccine. DC transduced with HD-AdV expressed higher levels of transgene-specific mRNA and up to 1200-fold higher levels of transgene protein than did DC transduced with a FG-AdV. In addition, HD-AdV-transduced DC stimulated superior transgene-specific CTL responses when administered in vivo, an effect that was further enhanced by maturing the DC with LPS prior to administration. In contrast to direct immunization with HD-AdV, vaccination with HD-AdV-transduced DC was associated with limited antibody responses against the AdV. We conclude that HD-AdV stimulates superior transgene-specific immune responses when compared to a FG-AdV, and that immunization with a DC-based vaccine maintains this efficacy while limiting antiviral reactivity. [ABSTRACT FROM AUTHOR]

We report the spectrum of ocular toxicity following accidental inoculation of latex of Calotropis procera (Sodom apple) in 29 eyes between January 2003 and December 2006. All patients presented with sudden painless dimness of vision with photophobia. Twenty-five (86%) patients had initial visual acuity of less than 20/60. All eyes had conjunctival congestion and mild to severe corneal edema with Descemet's folds. Three (10%) eyes had an epithelial defect, nine (31%) had iridocyclitis, and seven (24%) had associated secondary glaucoma. After treatment with topical corticosteroids, antiglaucoma agents, cycloplegics, hypertonic saline and tears supplements, 27 (93%) eyes recovered completely within 3-14 days. After three months, 17 (74%) out of 23 eyes showed a significant low endothelial cell count compared to the normal fellow eye ( P 0.001). The latex of Calotropis procera causes significant ocular morbidity which may be preventable by simple health education. The long-term effect on corneal endothelium has to be studied further. [ABSTRACT FROM AUTHOR]

The milky sap or latex of Euphorbia plant is highly toxic and an irritant to the skin and eye. This report illustrates the spectrum of ocular inflammation caused by accidental inoculation of latex of Euphorbia plant. Three patients presented with accidental ocular exposure to the milky sap of Euphorbia species of recent onset. The initial symptoms in all cases were severe burning sensation with blurring of vision. Visual acuity reduced from 20/60 to counting fingers. Clinical findings varied from kerato-conjunctivitis, mild to severe corneal edema, epithelial defects, anterior uveitis and secondary elevated intraocular pressure. All symptoms and signs had resolved by 10-14 days with active supportive medication. People who handle Euphorbia plants should wear eye protection. It is always advisable to ask the patient to bring a sample of the plant for identification. [ABSTRACT FROM AUTHOR]

To date, degraded mangrove ecosystem restoration accomplished worldwide primarily aligns towards rehabilitation with monotypic plantations, while ecological restoration principles are rarely followed in these interventions. However, researchers admit that most of these initiatives' success rate is not appreciable often. An integrative framework of ecological restoration for degraded mangroves where site-specific observations could be scientifically rationalized, with co-located reference pristine mangroves as the target ecosystem to achieve is currently distinctively lacking. Through this experimental scale study, we studied the suitability of site-specific strategies to ecologically restore degraded mangrove patches vis-à-vis the conventional mono-species plantations in a highly vulnerable mangrove ecosystem in Indian Sundarbans. This comprehensive restoration framework was trialed in small discrete degraded mangrove patches spanning ~ 65 ha. Site-specific key restoration components applied are statistically validated through RDA analyses and Bayesian t-tests. 25 quantifiable metrics evaluate the restoration success of a ~ 3 ha degraded mangrove patch with Ridgeline distribution, Kolmogorov-Smirnov (K-S) tests, and Mahalanobis Distance (D 2 ) measure to prove the site's near-equivalence to pristine reference in multiple ecosystem attributes. This restoration intervention irrevocably establishes the greater potential of this framework in the recovery of ecosystem functions and self-sustenance compared to that of predominant monoculture practices for vulnerable mangroves., (© 2024. The Author(s).)

Introduction: Biological nitrogen fixation (BNF), an unparalleled metabolic novelty among living microorganisms on earth, globally contributes ~88-101 Tg N year -1 to natural ecosystems, ~56% sourced from symbiotic BNF while ~22-45% derived from free-living nitrogen fixers (FLNF). The success of symbiotic BNF is largely dependent on its interaction with host-plant, however ubiquitous environmental heterotrophic FLNFs face many limitations in their immediate ecological niches to sustain unhindered BNF. The autotrophic FLNFs like cyanobacteria and oceanic heterotrophic diazotrophs have been well studied about their contrivances acclimated/adapted by these organisms to outwit the environmental constraints for functional diazotrophy. However, FLNF heterotrophs face more adversity in executing BNF under stressful estuarine/marine/aquatic habitats., Methods: In this study a large-scale cultivation-dependent investigation was accomplished with 190 NCBI accessioned and 45 non-accessioned heterotrophic FLNF cultivable bacterial isolates (total 235) from halophilic estuarine intertidal mangrove niches of Indian Sundarbans, a Ramsar site and UNESCO proclaimed World Heritage Site. Assuming ~1% culturability of the microbial community, the respective niches were also studied for representing actual bacterial diversity via cultivation-independent next-generation sequencing of V3-V4 rRNA regions., Results: Both the studies revealed a higher abundance of culturable Gammaproteobacteria followed by Firmicutes, the majority of 235 FLNFs studied belonging to these two classes. The FLNFs displayed comparable selection potential in media for free nitrogen fixers and iron-oxidizing bacteria, linking diazotrophy with iron oxidation, siderophore production, phosphorus solubilization, phosphorus uptake and accumulation as well as denitrification., Discussion: This observation validated the hypothesis that under extreme estuarine mangrove niches, diazotrophs are naturally selected as a specialized multidimensional entity, to expedite BNF and survive. Earlier metagenome data from mangrove niches demonstrated a microbial metabolic coupling among C, N, P, S, and Fe cycling in mangrove sediments, as an adaptive trait, evident with the co-abundant respective functional genes, which corroborates our findings in cultivation mode for multiple interrelated metabolic potential facilitating BNF in a challenging intertidal mangrove environment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mondal, Biswas, Chowdhury, Sengupta, Mandal, Kotal, Giri, Ghosh, Saha, Begam, Mukherjee, Das, Basak, Mitra Ghosh and Ray.)

Gigaxonin is an E3 ubiquitin ligase that plays a role in cytoskeletal stability. Its role in cancer is not yet clearly understood. Our previous studies of head and neck cancer had identified gigaxonin interacting with p16 for NFκB ubiquitination. To explore its role in cancer cell growth suppression, we analyzed normal and tumor DNA from cervical and head and neck cancers. There was a higher frequency of exon 8 SNP (c.1293 C>T, rs2608555) in the tumor (46% vs. 25% normal, P = 0.011) pointing to a relationship to cancer. Comparison of primary tumor with recurrence and metastasis did not reveal a statistical significance. Two cervical cancer cell lines, ME180 and HT3 harboring exon 8 SNP and showing T allele expression correlated with higher gigaxonin expression, reduced in vitro cell growth and enhanced cisplatin sensitivity in comparison with C allele expressing cancer cell lines. Loss of gigaxonin expression in ME180 cells through CRISPR-Cas9 or siRNA led to aggressive cancer cell growth including increased migration and Matrigel invasion. The in vitro cell growth phenotypes were reversed with re-expression of gigaxonin. Suppression of cell growth correlated with reduced Snail and increased e-cadherin expression. Mouse tail vein injection studies showed increased lung metastasis of cells with low gigaxonin expression and reduced metastasis with reexpression of gigaxonin. We have found an association between C allele expression and RNA instability and absence of multimeric protein formation. From our results, we conclude that gigaxonin expression is associated with suppression of epithelial-mesenchymal transition through inhibition of Snail., Significance: Our results suggest that GAN gene exon 8 SNP T allele expression correlates with higher gigaxonin expression and suppression of aggressive cancer cell growth. There is downregulation of Snail and upregulation of e-cadherin through NFκB ubiquitination. We hypothesize that exon 8 T allele and gigaxonin expression could serve as diagnostic markers of suppression of aggressive growth of head and neck cancer., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Background: Disease and therapy-related hypoproliferative thrombocytopenia is a significant barrier to managing acute lymphoblastic leukaemia (ALL) patients. To reduce the risk of haemorrhage, apheretic platelet transfusion is a modern, effective, and expensive option. Since most ALL patients in Bangladesh have financial constraints, this study can shed light on the magnitude of benefit regarding the effectiveness of apheretic platelet prophylactically and therapeutically in children of ALL receiving induction chemotherapy., Materials and Methods: This observational cross-sectional study was conducted in the department of transfusion medicine and the department of paediatric haematology and oncology at a tertiary level hospital in Bangladesh from June 2020 to June 2021. A total of 33 cases of ALL were enroled in this study according to inclusion and exclusion criteria. After receiving written informed consent, relevant data were collected using a face-to-face interview with the guardian of the patients, thorough clinical examination, and relevant investigation. After the collection of all the required data, analysis was done by Stata (v.16)., Results: Mean age of the patients was 7.39±4.46 (SD), ranging from 1 to 18 years. The majority of children were aged younger than or equal to 10 years (69.70%). Male children were slightly predominant (51.5%). Significant post-transfusion platelet increment (Median pre-transfusion count 16×10 3 /μl vs. Median post-transfusion count 133×10 3 /μl, P <0.001) was observed. WHO bleeding grades also improved after apheretic platelet transfusion ( P <0.05). Age was a significant factor associated with corrected count increment (CCI) in both univariate and multivariate analysis. In subgroup analysis, age and gender were significant predictors of CCI in therapeutic transfusion group but not in prophylactic transfusion group., Conclusions: Significant improvement in bleeding status and platelet count was observed following apheretic platelet transfusion., Competing Interests: The authors have declared that they have no competing interests.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

In the vicinity of the coast, predominantly groundwater is the sole reliable resource for potable purposes as the surface water sources are highly saline and unfit for human consumption. However, the groundwater in Sagar Island is highly vulnerable to saltwater intrusion. The majority of drinking water comes from government-owned hand pump-equipped tube wells. But during the summer season, many of these tube wells yield significantly less water. Hence, in the current scenario, water quality assessment has become important to the quantity available. Total of 31 samples of deep tube wells (groundwater) are collected at variegated locations during pre-monsoon season throughout Sagar, and then, the physical and chemical quality parameters of these water samples are analysed. Furthermore, a multivariate statistical technique is executed with the aid of the SPSS program. The hydro-chemical parameters that are taken into account for the quality analysis are pH, salinity, electrical conductivity (EC), total dissolved solids (TDS), total hardness, aluminium, arsenic, bi-carbonate, cadmium, iron, chloride, copper, chromium, cobalt, lead, magnesium, manganese, nickel, potassium, sulphate, zinc, and sodium. Then, the analysed data evaluates the water quality index (WQI). Five components are identified through the principal component analysis (PCA) technique, and 82.642% total variance is found. The outcomes of the quality assessment study illustrate that about 54.84% of collected samples come in the "excellent" water quality class when calculated by the "weighted arithmetic WQI method," and 90.32% of collected groundwater samples come in the "good" water quality class when computed using the "modified weighted arithmetic WQI method." This study helps for the interpretation of WQI to assess groundwater quality., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Bibenzyl derivatives comprising two benzene rings are secondary plant metabolites with significant therapeutic value. To date, bibenzyl derivatives in the Plant kingdom have been primarily identified in bryophytes, orchids, and Cannabis sativa . The metabolic cost investment by plant species for the synthesis of these bioactive secondary metabolites is rationalized as a mechanism of plant defense in response to oxidative stress induced by biotic/abiotic factors. Bibenzyl derivatives are synthesized from core phenylpropanoid biosynthetic pathway offshoots in plant species. Mangrove and mangrove associate species thrive under extreme ecological niches such as a hypersaline intertidal environment through unique adaptive and acclimative characteristics, primarily involving osmotic adjustments followed by oxidative stress abatement. Several primary/secondary bioactive metabolites in mangrove species have been identified as components of salinity stress adaptation/acclimation/mitigation; however, the existence of a bibenzyl scaffold in mangrove species functioning in this context remains unknown. We here report the confirmed detection of a core bibenzyl scaffold from extensive gas chromatography-mass spectrometry and gas chromatography-flame ionization detection analyses of 28 mangrove and mangrove associate species from the Indian Sundarbans. We speculate that the common presence of this bibenzyl core molecule in 28 mangrove and associate species may be related to its synthesis via branches of the phenylpropanoid biosynthetic pathway induced under high salinity, which functions to detoxify reactive oxygen species as a protection for the maintenance of plant metabolic processes. This finding reveals a new eco-physiological functional role of bibenzyls in unique mangrove ecosystem., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sarkar, Kotal, Giri, Mandal, Hudait, Madhu, Saha, Basak, Sengupta and Ray.)

Competing Interests: None

Liquid biopsies are gaining more traction as non-invasive tools for the diagnosis and monitoring of cancer. In a new paradigm of cancer treatment, a synergistic botanical drug combination (APG-157) consisting of multiple molecules, is emerging as a new class of cancer therapeutics, targeting multiple pathways and providing a durable clinical response, wide therapeutic window and high level of safety. Monitoring the efficacy of such drugs involves assessing multiple molecules and cellular events simultaneously. We report, for the first time, a methodology that uses circulating plasma cell-free RNA (cfRNA) as a sensitive indicator of patient response upon drug treatment. Plasma was collected from six patients with head and neck cancer (HNC) and four healthy controls receiving three doses of 100 or 200 mg APG-157 or placebo through an oral mucosal route, before treatment and on multiple points post-dosing. Circulating cfRNA was extracted from plasma at 0-, 3- and 24-hours post-treatment, followed by RNA sequencing. We performed comparative analyses of the circulating transcriptome and were able to detect significant perturbation following APG-157 treatment. Transcripts associated with inflammatory response, leukocyte activation and cytokine were upregulated upon treatment with APG-157 in cancer patients, but not in healthy or placebo-treated patients. A platelet-related transcriptional signature could be detected in cancer patients but not in healthy individuals, indicating a platelet-centric pathway involved in the development of HNC. These results from a Phase 1 study are a proof of principle of the utility of cfRNAs as non-invasive circulating biomarkers for monitoring the efficacy of APG-157 in HNC., Competing Interests: PM and LA are employees of Aveta Biomics Inc, which provided partial funding for the current study, and have a patent pending for Polypharmaceutical Drug Compositions and Related Methods. PM and LA had no role in the recruitment of the subjects and collection and analysis of the samples. All authors were blinded to the study and its results until the study was completed. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tosevska, Morselli, Basak, Avila, Mehta, Wang, Srivatsan and Pellegrini.)

We have observed overexpression of PACS-1, a cytosolic sorting protein in primary cervical tumors. Absence of exonic mutations and overexpression at the RNA level suggested a transcriptional and/or posttranscriptional regulation. University of California Santa Cruz genome browser analysis of PACS-1 micro RNAs (miR), revealed two 8-base target sequences at the 3' terminus for hsa-miR-34a and hsa-miR-449a. Quantitative RT-PCR and Northern blotting studies showed reduced or loss of expression of the two microRNAs in cervical cancer cell lines and primary tumors, indicating dysregulation of these two microRNAs in cervical cancer. Loss of PACS-1 with siRNA or exogenous expression of hsa-miR-34a or hsa-miR-449a in HeLa and SiHa cervical cancer cell lines resulted in DNA damage response, S-phase cell cycle arrest, and reduction in cell growth. Furthermore, the siRNA studies showed that loss of PACS-1 expression was accompanied by increased nuclear γH2AX expression, Lys 382 -p53 acetylation, and genomic instability. PACS-1 re-expression through LNA-hsa-anti-miR-34a or -449a or through PACS-1 cDNA transfection led to the reversal of DNA damage response and restoration of cell growth. Release of cells post 24-h serum starvation showed PACS-1 nuclear localization at G 1 -S phase of the cell cycle. Our results therefore indicate that the loss of hsa-miR-34a and hsa-miR-449a expression in cervical cancer leads to overexpression of PACS-1 and suppression of DNA damage response, resulting in the development of chemo-resistant tumors., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (Published in the U.S.A.)

Mass mortalities of the larval stage of the giant freshwater prawn, Macrobrachium rosenbergii , have been occurring in Bangladesh since 2011. Mortalities can reach 100% and have resulted in an 80% decline in the number of hatcheries actively producing M. rosenbergii . To investigate a causative agent for the mortalities, a disease challenge was carried out using infected material from a hatchery experiencing mortalities. Moribund larvae from the challenge were prepared for metatranscriptomic sequencing. De novo virus assembly revealed a 29 kb single‑stranded positive-sense RNA virus with similarities in key protein motif sequences to yellow head virus (YHV), an RNA virus that causes mass mortalities in marine shrimp aquaculture, and other viruses in the Nidovirales order. Primers were designed against the novel virus and used to screen cDNA from larvae sampled from hatcheries in the South of Bangladesh from two consecutive years. Larvae from all hatcheries screened from both years were positive by PCR for the novel virus, including larvae from a hatchery that at the point of sampling appeared healthy, but later experienced mortalities. These screens suggest that the virus is widespread in M. rosenbergii hatchery culture in southern Bangladesh, and that early detection of the virus can be achieved by PCR. The hypothesised protein motifs of Macrobrachium rosenbergii golda virus (MrGV) suggest that it is likely to be a new species within the Nidovirales order. Biosecurity measures should be taken in order to mitigate global spread through the movement of post-larvae within and between countries, which has previously been linked to other virus outbreaks in crustacean aquaculture.

Competing Interests: None

Competing Interests: None

Purpose: To analyze the overall clinical outcomes of Descemet membrane endothelial keratoplasty (DMEK) in 600 consecutive cases., Methods: Retrospective, consecutive interventional case series operated by a single surgeon. Six hundred consecutive eyes of 524 patients with endothelial dysfunctions of different etiologies scheduled for DMEK were included in this study. All donor tissues were prepared by the operating surgeon during the procedure, using McCarey Kaufman medium or Cornisol-preserved cornea with endothelial cell density (ECD) of ≥2500 cells/mm 2 . Indications, postoperative best spectacle-corrected visual acuity (BSCVA), ECD, endothelial cell loss (ECL), and complications were analyzed postoperatively between 3 months and 2 years., Results: The commonest indication was post-cataract corneal edema/bullous keratopathy in 262 (43.7%) eyes followed by Fuchs' endothelial corneal dystrophy 218 (36.3%). Vision affected comorbidities were present in 91 (15.2%) eyes. In phakic eyes with cataract (222; 37%), DMEK was combined with cataract surgery (Triple-DMEK). BSCVA of ≥20/25 was achieved in 41.0%, 46.4%, 49.2%, and 48.7% of eyes at 3, 6, 12, and 24 months, respectively and stabilized at 6 months (P = 0.54). Mean ECD decreased from 2884 ± 178 cells/mm 2 (n = 600) before surgery to 2223 ± 321 (n = 597), 2099 ± 354 (n = 524), 1918 ± 373 (n = 374), and 1772 ± 439 cells/mm 2 (n = 158) at 3, 6, 12, and 24 months respectively. The corresponding mean ECL was 22.9 ± 11.4%, 27.2 ± 12.4%, 33.5 ± 13.0%, and 38.6 ± 14.3%, respectively (P < 0.05 for all-time points). The commonest complication was DM detachment in 59 (9.8%) eyes of which 23 (3.8%) eyes required rebubbling. Three (0.5%) eyes had primary graft failure. Endothelial rejection occurred in 7 (1.2%) eyes until the last follow-up., Conclusion: DMEK is a safe and effective procedure in different types of endothelial diseases with encouraging surgical and clinical outcomes. Complications are less and ECL percentage up to 2 years is acceptable., Competing Interests: None

Sundarbans mangrove forest, the world's largest continuous mangrove forests expanding across India and Bangladesh, in recent times, is immensely threatened by degradation stress due to natural stressors and anthropogenic disturbances. The degradation across the 19 mangrove forests in Indian Sundarbans was evaluated by eight environmental criteria typical to mangrove ecosystem. In an attempt to find competent predictors for mangrove ecosystem degradation, key eco-physiological resilience trait complex specific for mangroves from 4922 individuals for physiological analyses with gene expression and 603 individuals for leaf tissue distributions from 16 mangroves and 15 associate species was assessed along the degradation gradient. The degradation data was apparently categorized into four and CDFA discriminates 97% of the eco-physiological resilience data into corresponding four groups. Predictive Bayesian regression models and mixed effects models indicate osmolyte accumulation and thickness of water storage tissue as primary predictors of each of the degradation criteria that appraise the degradation status of mangrove ecosystem. RDA analyses well represented response variables of degradation explained by explanatory resilience variables. We hypothesize that with the help of our predictive models the policy makers could trace even the cryptic process of mangrove degradation and save the respective forests in time by proposing appropriate action plans.

Conjunctival stromal tumour (COST) is a recently described rare conjunctival tumour of mesenchymal origin with only four publications describing a handful of cases thus far. In this report, we describe the anterior-segment optical coherence tomography (AS-OCT) characteristics in a case of COST for the first time, in addition to the clinical and histopathological characteristics. The AS-OCT showed an elevated, dome-shaped hyporeflective homogenous lesion in the conjunctival stroma lined by hyperreflective outer layer with mild posterior shadowing, consistent with histological description of a paucicellular tumour with large myxoid collagenous material inside. Immunohistochemistry showed positive CD34 and vimentin but negative S100 and smooth muscle actin, thereby differentiating it from conjunctival myxoma., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Recurrence of herpes simplex virus (HSV) keratitis is a problem of keratoplasty and the prognosis is often poor in spite of oral acyclovir (ACV) prophylaxis. This 64-year-old woman was a known case of recurrent HSV endotheliitis with irreversible corneal oedema in the left eye for 2 years. She underwent Descemet membrane endothelial keratoplasty with intraocular lens implantation under perioperative oral ACV and prednisolone. After 4 weeks, her cornea cleared with the best-corrected vision of 6/9. After 2.5 months, she presented with sudden photophobia and visual loss. An increasing focal endothelial lesion was noticed even after oral ACV. Suspecting fungal interface infection, anterior chamber tap was done for PCR for panfungal and viruses. It was only positive for HSV. Oral ACV was changed to oral valacyclovir. The patient responded dramatically within 2 weeks, and after 12 weeks, the lesion disappeared completely, leaving behind a faint scar with 6/9 p vision. Oral valacyclovir, a prodrug of ACV, may work better than oral ACV., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Descemet Membrane Endothelial Keratoplasty (DMEK) is now becoming the popular form of endothelial keratoplasty using only donor DM with healthy endothelium as true component lamellar corneal surgery., Objective: To analyze the results of visual outcomes, endothelial cell loss and complications of Descemet membrane endothelial keratoplasty in first consecutive 100 Indian eyes., Methods: 100 eyes of 95 consecutive patients with endothelial dysfunctions of different etiologies scheduled for DMEK, were included in this study. In each case, surgeon prepared tissue using McCarey Kaufman medium- or Cornisol-preserved donor cornea with a cell count of ≥2500 cells/mm 2 . Surgical complications, Best Spectacle Corrected Visual Acuity (BSCVA); Endothelial Cell Density (ECD) and Endothelial Cell Loss (ECL) were analyzed for each patient after a minimum follow-up of three months., Results: The Main indication was pseudophakic corneal edema or bullous keratopathy in 52 (52%) eyes. 38 (38%) eyes had Fuchs' dystrophy with various grades of cataract. In 43 phakic eyes, DMEK was combined with cataract surgery and intraocular lens implantation. Mean DM-roll preparation time was 7.5 ± 2.8 min and in 3 eyes, DM-graft were damaged. After 3-months, BSCVA was ≥20/25 in 57 (57.6%) cases. Mean ECD was 2123 ± 438/mm 2 (range: 976 - 3208/ mm 2 ) and the mean endothelial cell loss after 3-months was 26.92 ± 13.40 (range: 4.90 - 66.6%). Partial DM detachment occurred in 8 (8.0%) eyes and rebubbling required in 4 eyes. Iatrogenic primary graft failure occurred in one eye., Conclusion: Descemet membrane endothelial keratoplasty is a safe and effective procedure in several types of endothelial diseases among Indian patients with encouraging surgical and visual outcomes. Complications are less and endothelial cell loss percentage is acceptable.

Diseases have been recognized as the major obstacle to the shrimp ( Penaeus monodon ) and prawn ( Macrobrachium rosenbergii ) aquaculture production in Bangladesh. This study provides an assessment of shrimp and prawn diseases/syndromes, health management practices, and occupational health hazards associated with the handling of chemical and biological products to prevent and treat shrimp and prawn diseases. A survey was conducted using a semi-structured questionnaire with 380 shrimp and prawn farmers in the southwest of Bangladesh during February and June of 2016. The farms were categorized on the basis of the three cropping patterns: shrimp polyculture, prawn polyculture, and shrimp and prawn polyculture. Eight different diseases and/or symptoms were reported by the surveyed farmers. The white spot disease and the broken antenna and rostrum symptom were the most common in shrimp and prawn species, respectively. In total, 35 chemical and biological products (4 antibiotics, 15 disinfectants, 13 pesticides, 2 feed additives and probiotics) were used to treat and/or prevent diseases in the all farm categories. The major constraints for disease management were limited access to disease diagnostic service, inadequate product application information and lack of knowledge on better management practices. Handling chemicals and preparation of medicated feed with bare hands was identified as a potential occupational health hazard. This study suggests improvements in farmers' knowledge and skill in disease diagnostics and health management practices, and appropriate handling of potentially hazardous chemicals., (© 2018 The Authors.)

Purpose: To compare the serology profile of donors from Hospital Cornea Retrieval Programme-donors (HCRP-D) and voluntary cornea donors (VC-D) from a large eye bank in Eastern India., Methods: This is a retrospective analysis of donor details from January 2011 to December 2016. Donor demographics, cause of death, and serology reports were compiled. Postmortem blood was tested for human immunodeficiency virus 1 and 2 (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis using government-approved kits as per the National Programme for Control of Blindness Standards of Eye Banking. Donors for whom serology was not possible were excluded., Results: A total of 4300 of 4353 donors were included of which 74.3% were hospital donors and 25.7% were voluntary donors. A total of 93 (2.2%) donors with 94 seropositive reports were noted: 79 (84.9%) from HCRP-D and 14 (15.1%) from VC-D which was statistically significantly higher (P = 0.02). Among seropositive reports, HIV, HBV, HCV, and syphilis accounted for 12 (12.8%), 38 (40.4%), 36 (38.3%), and eight (8.5%), respectively. There was no correlation between the cause of death and seropositivity. A statistically significant decreasing trend in seroprevalence among hospital donors was observed over the years (5.3% in 2011 to 1.4% in 2016; P = 0.004). Two (0.47%) of 421 hospital donors with prior negative serology were found to be seropositive., Conclusion: Seropositive rates are significantly higher among hospital donors in spite of medical prescreening compared to nonscreened voluntary donors. Serology should be repeated even when prior reports are available.

PurposeThe purpose of the study was to evaluate the efficacy and safety of intravitreal pirfenidone for inhibition of proliferative vitreoretinopathy (PVR) in a model of penetrating ocular injury.Patients and methodsPenetrating trauma was induced on the retina of rabbit and treated either with 0.1 ml of phosphate-buffered saline (PBS) or 0.1 ml of 0.5% pirfenidone, and development of PVR was evaluated clinically and graded after 1 month. Histopathology and immunohistochemistry with transforming growth factor beta (TGFβ), alpha smooth muscle actin (αSMA), and collagen-1 were performed to assess the fibrotic changes. Expression of cytokines in the vitro-retinal tissues at different time points following pirfenidone and PBS injection was examined by RT-PCR. Availability of pirfenidone in the vitreous of rabbit at various time points was determined by high-performance liquid chromatography following injection of 0.1 ml of 0.5% pirfenidone. In normal rabbit eye, 0.1 ml of 0.5% pirfenidone was injected to evaluate any toxic effect.ResultsClinical assessment and grading revealed prevention of PVR formation in pirfenidone-treated animals, gross histology, and histopathology confirmed the observation. Immunohistochemistry showed prevention in the expression of collagen-I, αSMA, and TGFβ in the pirfenidone-treated eyes compared to the PBS-treated eyes. Pirfenidone inhibited increased gene expression of cytokines observed in control eyes. Pirfenidone could be detected up to 48 h in the vitreous of rabbit eye following single intravitreal injection. Pirfenidone did not show any adverse effect following intravitreal injection; eyes were devoid of any abnormal clinical sign, intraocular pressure, and electroretinography did not show any significant change and histology of retina remained unchanged.ConclusionThis animal study shows that pirfenidone might be a potential therapy for PVR. Further clinical study will be useful to evaluate the clinical application of pirfenidone.

Purpose: To know the perception of young ophthalmologists about their dissertation and academics during residency training in order to improve the research output during present residency programs in India., Methods: A survey was conducted by Academic and Research Committee of the All India Ophthalmological Society, the world's second largest ophthalmic professional's organization, in 2014-2016 of young ophthalmologists (those who completed residency between 2005 and 2012) to gauge usefulness of dissertation or thesis during postgraduate residency., Results: There were 1005 respondents, of whom 531 fulfilled inclusion criteria. On a scale of 0-10, residents rated level of supervision of their dissertation as adequate (mean 5.9/10, standard deviation [SD] = 3.1, median = 6). The level of infrastructure available was for dissertation rated as 5.9/10 (median = 7, SD = 3.1), and 6.2/10 was the score that residents said about value added by the dissertation (median = 7). The dissertation was presented at local (33.5%), state (28.1%), national (15.4%), and international (4%) levels. Students, not supervisors, did most of the local and state level presentations. It was published in some forms at local 210 (39.5%), state (140, 26.4%), national (94, 17.7%), and international (39, 7.3%) levels. On a scale of 0-4, seminars (3/4) and case presentations were (3/4) rated higher than didactic lectures (2.2/4), journal clubs (2.2/4), and wet laboratory (1.1/4)., Conclusion: Peer-reviewed publications from Indian residency training dissertations were few. Residents felt dissertation added value to their training, but there was a huge range among the responses. Journal clubs and wet laboratories were not graded high in academic programs, unlike seminars and case presentations.

We and others have shown that the cystatin E/M gene is inactivated in primary human tumors, pointing to its role as a tumor suppressor gene. However, the molecular mechanism of tumor suppression is not yet understood. Using plasmid-directed cystatin E/M gene overexpression, a lentivirus-mediated tetracycline-inducible vector system, and human papillomavirus 16 (HPV 16) E6 and E7 gene-immortalized normal human epidermal keratinocytes, we demonstrated intracellular and non-cell-autonomous apoptotic growth inhibition of tumor cell lines and that growth inhibition is associated with cytoplasmic retention of NF-κB. We further demonstrated decreased phosphorylation of IκB kinase (IKKβ) and IκBα in the presence of tumor necrosis factor alpha (TNF-α), confirming the role of cystatin E/M in the regulation of the NF-κB signaling pathway. Growth suppression of nude mouse xenograft tumors carrying a tetracycline-inducible vector system was observed with the addition of doxycycline in drinking water, confirming that the cystatin E/M gene is a tumor suppressor gene. Finally, immunohistochemical analyses of cervical carcinoma in situ and primary tumors have shown a statistically significant inverse relationship between the expression of cystatin E/M and cathepsin L and a direct relationship between the loss of cystatin E/M expression and nuclear expression of NF-κB. We therefore propose that the cystatin E/M suppressor gene plays an important role in the regulation of NF-κB., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer, with 600,000 new cases every year worldwide. Although chemotherapeutics exist, five-year survival is only 50%. New strategies to overcome drug resistance are required to improve HNSCC treatment. Curcumin-difluorinated (CDF), a synthetic analog of curcumin, was packaged in liposomes and used to evaluate growth inhibition of cisplatin resistant HNSCC cell lines CCL-23R and UM-SCC-1R generated from the parental cell lines CCL-23 and UM-SCC-1 respectively. Growth inhibition in vitro and expression levels of the CD44 (cancer stem cell marker), cytokines, and growth factors were investigated after liposomal CDF treatment. The in vivo growth inhibitory effect of liposomal CDF was evaluated in the nude mice xenograft tumor model of UM-SCC-1R and the inhibition of CD44 was measured. Treatment of the resistant cell lines in vitro with liposomal CDF resulted in a statistically significant growth inhibition (p < 0.05). The nude mice xenograft study showed a statistically significant tumor growth inhibition of UM-SCC-1R cells and a reduction in the expression of CD44 (p < 0.05), indicating an inhibitory effect of liposomal CDF on CSCs. Our results demonstrate that delivery of CDF through liposomes may be an effective method for the treatment of cisplatin resistant HNSCC.

The molecular mechanism of p16-mediated senescence in cisplatin-treated cancer cells is not fully understood. Here we show that cisplatin treatment of head and neck cancer cells results in nuclear transport of p16 leading to a molecular modification of NFκB. Chromatin immunoprecipitation assays show that this modification is associated with the inhibition of NFκB interacting with its DNA binding sequences, leading to decreased expression of NFκB-transcribed proteins. LCMS proteomic analysis of LAP-TAP-purified proteins from HeLa cells containing a tetracycline-inducible GFP-S peptide-NFκB expression system identified gigaxonin, an ubiquitin E3 ligase adaptor, as an NFκB-interacting protein. Immunoblotting and siRNA studies confirmed the NFκB-gigaxonin interaction and the dependence of this binding on p16-NFκB binding. Using gel shift assays, we have confirmed p16-NFκB and gigaxonin-NFκB interactions. Furthermore, we have observed increased NFκB ubiquitination with cisplatin treatment that is abolished in the absence of p16 and gigaxonin expression. Analysis of 103 primary tumors has shown that increased nuclear p16 expression correlates with enhanced survival of head and neck cancer patients (p < 0.0000542), indicating the importance of nuclear p16 expression in prognosis. Finally, p16 expression is associated with reduced cytokine expression and the presence of human papilloma virus in chemoradiation-sensitive basaloid tumors. However, the absence of p16 expression is associated with enhanced cytokine expression and the absence of human papilloma virus in aggressive tumors. These results clearly demonstrate that nuclear p16 and gigaxonin play an important role in chemosensitivity of head and neck cancers through ubiquitination of NFκB., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

Purpose: To analyze the complications and their managements in Descemet's stripping endothelial keratoplasty (DSEK) in consecutive 430 cases by single surgeon in a tertiary eye hospital., Materials and Methods: 430 eyes of 366 patients with endothelial dysfunctions scheduled for DSEK, were analyzed retrospectively. In all cases donor dissection was performed manually, and 'Taco' insertion and unfolding technique was used. Intra-operative and postoperative complications with their managements and outcomes were reviewed retrospectively. Periodic endothelial cell density was analyzed for each patient till the last visit. Follow-up period was between 3 to 60 months (mean 18.7 months)., Results: 13 (3.0%) eyes had operative complications during donor dissection and 16 (3.7%) had during recipient procedure. In 7 (1.6%) eyes, donor lenticule was replaced with a new one during the surgery. In early postoperative period, 21 (4.9%) eyes had donor dislocation and 12 (2.8%) eyes had air-induced pupillary block; and they were managed immediately. 2 cases had primary graft failure and in 1 case had postoperative bacterial endophthalmitis requiring evisceration. In late postoperative period, 48 (11.3%) eyes had secondary glaucoma and 14 (3.3%) eyes had late secondary graft failure. Endothelial rejection occurred in 5 (1.2%) cases. Mean endothelial cell loss was 19.7% after 3 months and 54.2% after 5 years. Total graft failure in this series was 31 (7.2%) and in 17 cases re-DSEK was performed successfully., Conclusions: Both operative and postoperative complications do occur in DSEK. Most of these complications can be managed by medical or appropriate surgical means. Some of the complications can be avoided and reduced with experience.

Cellular heterogeneity is an integral part of cancer development and progression. Progression can be associated with emergence of cells that exhibit high phenotypic plasticity (including "de-differentiation" to primitive developmental states), and aggressive behavioral properties (including high tumorigenic potentials). We observed that many biomarkers that are used to identify Cancer Stem Cells (CSC) can label cell subsets in an advanced clinical stage of lung cancer (malignant pleural effusions, or MPE). Thus, CSC-biomarkers may be useful for live sorting functionally distinct cell subsets from individual tumors, which may enable investigators to hone in on the molecular basis for functional heterogeneity. We demonstrate that the CD44(hi) (CD44-high) cancer cell subsets display higher clonal, colony forming potential than CD44(lo) cells (n=3) and are also tumorigenic (n=2/2) when transplanted in mouse xenograft model. The CD44(hi) subsets express different levels of embryonal (de-differentiation) markers or chromatin regulators. In archived lung cancer tissues, ALDH markers co-localize more with CD44 in squamous cell carcinoma (n=5/7) than Adeno Carcinoma (n=1/12). MPE cancer cells and a lung cancer cell line (NCI-H-2122) exhibit chromosomal abnormalities and 1p36 deletion (n=3/3). Since miR-34a maps to the 1p36 deletion site, low miR-34a expression levels were detected in these cells. The colony forming efficiency of CD44(hi) cells, characteristic property of CSC, can be inhibited by mir-34a replacement in these samples. In addition the highly tumorigenic CD44(hi) cells are enriched for cells in the G2 phase of cell cycle.

Purpose: To evaluate the effect of ethylenediaminetetraacetic acid (EDTA) on posterior capsular opacification (PCO) of rabbits and to assess its effect on intraocular tissues., Methods: Modulation of matrix metalloproteinase (MMP) activity in the aqueous following cataract surgery in rabbits and its prevention by different doses of EDTA was determined by zymography. For evaluation of PCO, lensectomized rabbits were intracamerally injected with single dose of either 5 mg EDTA or normal saline. After one month, the degree of PCO was determined by slitlamp biomicroscopy, Miyake-Apple view, and histology of the lens capsule. The effect of EDTA on intra ocular pressure (IOP), corneal endothelial cells, and the retina was evaluated by tonometry, specular microscopy and scanning electron microscopy, and electroretinography. The concentration of EDTA in the aqueous was determined by high performance liquid chromatography (HPLC) at different time points., Results: The MMP activity was significantly increased in the aqueous of the operated eyes, and EDTA reduced the degree of increase in a dose-dependent manner. EDTA treatment significantly reduced the degree of PCO (p<0.05). Histopathology of the lens capsule showed a reduction in the number of proliferating and migrating cells as well as MMP2 expression in the EDTA-treated eyes. EDTA treatment did not change the IOP; density, morphology and ultrastructure of the corneal endothelial cells; and electroretinography (ERG). EDTA was detectable in the aqueous humor up to 72 h following a single intracameral injection., Conclusions: EDTA reduces the degree of PCO by suppressing the MMP activity and it is not toxic to intra ocular structures at the concentration used.

Purpose: To determine whether curcumin would inhibit IκB kinase β (IKKβ) kinase activity and suppress expression of proinflammatory cytokines in head and neck squamous cell carcinoma cancer (HNSCC) patients., Experimental Design: Saliva was collected before and after subjects chewed curcumin tablets. Protein was extracted and IKKβ kinase activity measured. Interleukin (IL)-6 and IL-8 levels in the salivary supernatants were measured by ELISA. IL-6, IL-8, and other interleukin were also measured independently with ELISA to confirm the inhibitory effect of curcumin on expression and secretion of salivary cytokines., Results: Curcumin treatment led to a reduction in IKKβ kinase activity in the salivary cells of HNSCC patients (P < 0.05). Treatment of UM-SCC1 cells with curcumin as well as with post-curcumin salivary supernatant showed a reduction of IKKβ kinase activity. Significant reduction of IL-8 levels (P < 0.05) was seen in post-curcumin samples from patients with dental caries. Although there was reduced IL-8 expression in 8 of 21 post-curcumin samples of HNSCC patients, the data did not reach statistical significance. Saliva samples from HNSCC patients were also analyzed in a blinded fashion for expression of cytokines. IL-10, IFN-γ, IL-12p70, and IL-2 clustered together, and granulocyte macrophage colony stimulating factor and TNF-α clustered together. Log₁₀ ratio analysis showed decrease in expression of all nine cytokines in both the salivary supernatant and salivary cells of curcumin-treated samples., Conclusions: Curcumin inhibited IKKβ kinase activity in the saliva of HNSCC patients, and this inhibition correlated with reduced expression of a number of cytokines. IKKβ kinase could be a useful biomarker for detecting the effect of curcumin in head and neck cancer., (©2011 AACR.)

Malignant Pleural Effusions (MPE) may be useful as a model to study hierarchical progression of cancer and/or intratumoral heterogeneity. To strengthen the rationale for developing the MPE-model for these purposes, we set out to find evidence for the presence of cancer stem cells (CSC) in MPE and demonstrate an ability to sustain intratumoral heterogeneity in MPE-primary cultures. Our studies show that candidate lung CSC-expression signatures (PTEN, OCT4, hTERT, Bmi1, EZH2 and SUZ12) are evident in cell pellets isolated from MPE, and MPE-cytopathology also labels candidate-CSC (CD44, cMET, MDR-1, ALDH) subpopulations. Moreover, in primary cultures that use MPE as the source of both tumor cells and the tumor microenvironment (TME), candidate CSC are maintained over time. This allows us to live-sort candidate CSC-fractions from the MPE-tumor mix on the basis of surface markers (CD44, c-MET, uPAR, MDR-1) or differences in xenobiotic metabolism (ALDH). Thus, MPE-primary cultures provide an avenue to extract candidate CSC populations from individual (isogenic) MPE-tumors. This will allow us to test whether these cells can be discriminated in functional bioassays. Tumor heterogeneity in MPE-primary cultures is evidenced by variable immunolabeling, differences in colony-morphology, and differences in proliferation rates of cell subpopulations. Collectively, these data justify the ongoing development of the MPE-model for the investigation of intratumoral heterogeneity, tumor-TME interactions, and phenotypic validation of candidate lung CSC, in addition to providing direction for the pre-clinical development of rational therapeutics.

Purpose: To analyze the results of Descemet stripping and endothelial keratoplasty (DSEK) in the first consecutive 75 cases., Materials and Methods: Prospective, non-randomized, non-comparative interventional case series. Seventy-five eyes of 75 patients with endothelial dysfunctions of different etiology, scheduled for DSEK, were included in this study. Healthy donor cornea with a cell count of> 2000 cells/sq mm was considered for transplantation in each case. Indications, operative problems and postoperative complications were noted. Best corrected visual acuity (BCVA), refractive and keratometric astigmatism, central corneal thickness (CCT) and endothelial cell density (ECD) were analyzed for each patient after a minimum follow-up of three months., Results: Main indication was pseudophakic corneal edema and bullous keratopathy in 53 (70.7%) eyes. Seventeen (22.7%) cases had moderate to severe Fuchs' dystrophy with various grades of cataract; and DSEK was combined with manual small-incision cataract surgery (MSICS) with posterior chamber intraocular lens (PCIOL) in those cases. After three months, BCVA was 20/60 or better in 62 (82.7%) cases. Mean refractive and keratometric astigmatism were 1.10 +/- 0.55 diopter cylinder (DCyl) and 1.24 +/- 0.92 DCyl. The CCT and ECD were 670.8 +/- 0.32 microm and 1485.6 +/- 168.6/sq mm respectively. The mean endothelial cell loss after three months was 26.8 +/- 4.24% (range: 13.3-38.4%). Dislocation of donor lenticule occurred in six (8.0%) eyes. Graft failure occurred in one case., Conclusions: Descemet stripping and endothelial keratoplasty is a safe and effective procedure in patients with endothelial dysfunctions with encouraging surgical and visual outcomes. It can be safely combined with MSICS with PCIOL in patients with moderate to severe Fuchs' dystrophy with cataract.

We present three cases of persistent corneal edema secondary to presumed dead adult filarial worms lying in the anterior chamber with their attachment to the endothelium. Two of them were initially diagnosed as descemet's fold with corneal edema. Two patients underwent penetrating keratoplasty and in one case, surgical removal was partly possible with clearing of cornea.

Dendritic cells (DC) play a central role in antigen presentation and are often targeted by adenoviral (Ad)-based gene therapy. However, DC lack the coxsackie-Ad receptor, and little is known about the process by which they acquire and present Ad-encoded antigens. We examined the expression of alpha(v)beta3 integrins (CD51/CD61) on mouse bone marrow-derived DC (BM-DC) and their susceptibility to transduction by Ad vectors. Less than 10% of BM-DC precursors expressed CD51, but expression increased over time in culture with granulocyte macrophage-colony stimulating factor (GM-CSF)/interleukin (IL)-4. After 7 days, 28 +/- 1.7% of CD11c+ DC expressed high levels of CD51 (CD51(hi)), and the remaining DC expressed low levels of CD51 (CD51(lo)). CD51(hi) CD express higher major histocompatibility complex type 1 (MHC I); however, both of the DC subsets expressed similar levels of MHC II and costimulatory molecules. When exposed to a first-generation Ad vector, transgene expression was restricted to the CD51(hi) DC subset and blocked by soluble peptides expressing an arginine, glycine, aspartic acid (RGD) sequence, confirming the role of integrins in viral entry. Consistent with this, a modified Ad expressing an RGD-binding sequence in its fiber knob (Ad-RGD) transduced the CD51(hi) DC subset with significantly higher efficiency. When BM-DC were transduced with an Ad-expressing ovalbumin (Ad-OVA), the CD51(hi) subset proved superior in activating OT-I (T cell receptor-OVA) T cells. Similar to in vitro effects, systemic administration of GM-CSF/IL-4 increased the expression of CD51 on splenic DC and rendered these cells susceptible to Ad transduction. These results suggest that a limited subset of DC expressing high levels of alpha(v)beta3 integrins is preferentially transduced by Ad vectors and activates CD8+ T cell responses against Ad-encoded antigens.

Purpose: To determine the epidemiological pattern and risk factors involved in suppurative corneal ulceration in Gangetic West Bengal, eastern India, and to identify the specific microbial agents responsible for corneal infections., Methods: All patients with suspected microbial keratitis presenting to the corneal clinic at Disha Eye Hospital, Barrackpore, West Bengal, India, from January 2001 to December 2003 were evaluated. Sociodemographic data and information pertaining to the risk factors were recorded. After diagnosing infective corneal ulcer clinically, corneal scraping and cultures were performed., Results: Over a three-year period, 1198 patients with suppurative keratitis were evaluated. Ocular trauma was the most common predisposing factor in 994 (82.9%) patients (P< 0.0001), followed by use of topical corticosteroids in 231 (19.28%) patients. Cultures were positive in 811 (67.7%) patients. Among these culture positive cases, 509 (62.7%) patients had pure fungal infections (P< 0.001), 184 (22.7%) patients had pure bacterial infections and 114 (14.1%) had mixed fungal with bacterial infections. Acanthamoeba was detected in 4 (0.49%) patients. The most common fungal pathogen was Aspergillus spp representing 373 (59.8%) of all positive fungal cultures (P< 0.0001), followed by Fusarium spp in 132 (21.2%) instances. Most common bacterial isolate was Staphylococcus aureus, representing 127 (42.6%) of all the bacterial culture (P< 0.0001) followed by Pseudomonas spp 63 (21.1%)., Conclusion: Suppurative keratitis in Gangetic West Bengal, most often occurs after a superficial corneal trauma with vegetative or organic materials. Fungal ulcers are more common than bacterial ulcers. Aspergillus spp and Staphylococcus aureus were the most common fungus and bacteria respectively. These "regional" findings have important public health implications for the treatment and prevention of suppurative corneal ulceration in this region of India.

Specular microscopic study on clear corneal grafts indicates that at times surprisingly low endothelial cell density can maintain the grafted cornea in a relatively dehydrated state. The critical limit of the endothelial cell count for corneal decompensation is thought to be 700 cells/mm2. This communication reports 13 cases of clear corneal graft with endothelial cell count below 700 cells/mm2.

Intraocular infestation by live Gnathostoma spinigerum is a rare occurrence in humans. Most of the published reports are from South-East Asia. We report a case of intravitreal gnathostomiasis, where the worm was removed live and intact by pars plana vitrectomy.

Dendritic cells (DCs) are rare antigen-presenting cells that play a central role in stimulating immune responses. The combination of recombinant granulocyte macrophage-colony-stimulating factor (rGM-CSF) and recombinant interleukin-4 (rIL-4) provides an important stimulus for generating DCs from murine bone marrow precursors in vitro. Using miniature osmotic pumps, we now demonstrate that continuous infusion of these cytokines for 7 days had a similar effect in vivo, increasing the number and function of splenic DCs. Administration of rGM-CSF/rIL-4 (10 microg/d each) increased the concentration of CD11(+) DCs by 2.7-fold and the absolute number of splenic DCs by an average of 5.7-fold. DC number also increased in peripheral blood and lymph nodes. The resultant DCs exhibited a different phenotype and function than those in control mice or mice treated with rGM-CSF alone. rGM-CSF/IL-4 increased both the myeloid (CD11c(+)/CD11b(+)) and the lymphoid (CD11c(+)/CD8alpha(+)) subpopulations, whereas rGM-CSF increased only myeloid DCs. DCs were highly concentrated in the T-cell areas of white pulp after rGM-CSF/IL-4 administration, whereas they were diffusely distributed throughout white pulp, marginal zones, and red pulp in mice treated with rGM-CSF alone. rGM-CSF/rIL-4 also significantly increased the expression of major histocompatibility complex (MHC) class I and MHC class II on CD11c(+) cells and increased their capacity to take up antigens by macropinocytosis and receptor-mediated endocytosis. Splenic DCs generated in response to rGM-CSF/rIL-4 were functionally immature in terms of allostimulatory activity, but this activity increased after short-term in vitro culture. Systemic treatment with rGM-CSF/rIL-4 enhanced the response to an adenoviral-based vaccine and led to antigen-specific retardation in the growth of established tumor. We conclude that systemic therapy with the combination of rGM-CSF/rIL-4 provides a new approach for generating DCs in vivo.

Pellucid marginal degeneration (PMD) is a rare and usually a bilateral condition. We report a case of typical PMD with a unilateral presentation.